Regulation and function of class A Penicillin-binding proteins

•Class A PBPs are essential in most bacteria.•They provide a major contribution to overall PG synthesis during growth and cell division.•Multiple protein? protein interactions regulate the activity of class A PBPs.•E. coli PBP1B has additional essential roles under different stress conditions. Most bacteria surround their cell membrane with a peptidoglycan sacculus that counteracts the turgor and maintains the shape of the cell. Class A PBPs are bi-functional glycosyltransferase-transpeptidases that polymerize glycan chains and cross-link peptides. They have a major contribution to the total peptidoglycan synthesized during cell growth and cell division. In recent years it became apparent that class A PBPs participate in multiple protein? protein interactions and that some of these regulate their activities. In this opinion article, we review and discuss the role of class A PBPs in peptidoglycan growth and repair. We hypothesize that class A PBP function is essential in walled bacteria unless they have (a) SEDS protein(s) capable of replacing their function.